Celecoxib excretion

Plasma peak concentrations are achieved within 2 h and the elimination half-life is about 12 h. Within the clinical dose range, there is high plasma protein binding ( 97%). Celecoxib is metabolized primarily via cytochrome P450 2C9 to three inactive main metabolites. It is excreted in faeces ( 57%) and urine ( 27%) as determined by administration of a single oral dose of radiolabeled drug. Celecoxib is given orally (200-400 mg/day). 

Pharmacokinetics Celecoxib is readily absorbed, reaching a peak concentration in about three hours. It is extensively metabolized in the liver by cytochrome P-450 (CYP2C9), and is excreted in the feces and urine. Its half-life is about eleven hours, thus the drug is usually taken once a day. 

A 43-year-old woman with rheumatoid arthritis developed dizziness having taken celecoxib 200 mg/day for 2 weeks. At the start of treatment she had normal renal function (104). Her serum creatinine was 670 pmol/l (7.4 mg/dl) and blood urea nitrogen 30 mmol/1 (90 mg/dl). Creatinine clearance was 16 ml/minute. Urinalysis was normal and casts were not present. Urinary chemical analysis showed a sodium concentration of 18 mmol/1, a fractional excretion of sodium of 0.3, and a renal failure index of 0.493, consistent with prerenal acute renal insufficiency. Celecoxib was withdrawn. Although her renal function then improved, her serum creatinine was still abnormal (4.7 mg/dl) 1 month later. 

Example celecoxib (Celebrex), Bextric and Vioxx (removed by the FDA) Route PO Pregnancy category B Pharmacokinetic Absorbed from the GI tract, metabolized in the liver and primarily excreted in urine PB 97%... 

Paulson S K, Zhang J Y, lessen S M, et al. (2000). Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog, cynomolgus monkey and rhesus monkey. Xenobiotica. 30 731-744. 

C. Pharmacokinetics. NSAIDs are generally well absorbed, and volumes of distribution (Vd) are relatively small (eg, 0.15 L/kg for ibuprofen). COX-2 inhibitors have larger volumes of distribution (86-91 L in adults for rofecoxib, 400 L for celecoxib). Most agents are highly protein bound, and most are eliminated through hepatic metabolism and renal excretion with variable half-lives (eg, 1.5-2.5 hours for ibuprofen and 12-17 hours for naproxen). (See also Table 11-59.)... 

Celecoxib is ehminated predominantly by hepatic metabolism with httle imchanged drug recovered in the urine and feces. Fifty-seven percent of the dose was excreted in the feces and 27% was excreted in the urine. As a result, the daily recommended dose of celecoxib should be reduced by 50% in patients with moderate hepatic impairment (Child-Pugh Class B) [1]. 

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